Aims/hypothesis: Interleukin-1beta is a putative mediator of pancreatic beta-cell dysfunction and damage in Type I (insulin-dependent) diabetes mellitus. To better understand the molecular mechanisms involved in IL-1beta effects, we carried out a differential display of mRNA by RT-PCR to identify novel cytokine-regulated genes.
Methods: Fluorescence activated cell sorting-purified rat pancreatic beta-cells were exposed for 6 or 24 h to IL-1beta. Differentially expressed cDNA bands were cloned and then identified by comparing their sequences with data from the GenBank. Differential gene expression was confirmed by RT-PCR using specific primers.
Results: Interleukin-1beta increased the expression of adenine nucleotide translocator-1, phospholipase D-1 and cytokine-induced neutrophil chemoattractant-1 and decreased expression of the protein tyrosine phosphatase-like protein IA-2. Interleukin-1beta-induced differential expression of these genes in beta cells was confirmed by RT-PCR. In additional studies, IL-1beta was shown to induce chemokines other than cytokine-induced neutrophil chemoattractant-1, including cytokine-induced neutrophil chemoattractant-3 and monocyte chemotactic protein-1.
Conclusion/interpretation: Our observations indicate that IL-1beta modifies the expression of several genes in pancreatic beta cells. These genes may affect both function, viability and beta-cell recognition by the immune system. Functional characterization of the mRNAs which have been identified could facilitate a better understanding of the mechanisms leading to beta-cell destruction in Type I diabetes. [Diabetologia (1999) 42: 1199-1203]